DEAD-box protein DDX3 associates with eIF4F to promote translation of selected mRNAs

Soto-Rifo, Ricardo; Rubilar, Paulina S.; Limousin, Taran; Breyne, Sylvain de; Décimo, Didier; Ohlmann, Théophile

doi:10.1038/emboj.2012.220

Cited by 238 publications

(353 citation statements)

References 59 publications

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“…98 The DEAD-box helicase DDX3 is not essential for global translation, but is required for the translation of specific transcripts (e.g., Cyclin E1) that contain secondary structures within their 5' UTRs. 99,100 We found that mTOR promotes the recruitment of DDX3 to the 5' mRNA cap in a 4E-BP1/2-dependent manner, 72 suggesting a mechanism whereby mTOR activity is required for the translation of DDX3-bound transcripts. DDX6 (also known as RCK or p54) is a highly conserved DEAD-box helicase that contributes to global and transcript-specific mRNA storage, translational repression, and decay.…”

Section: Mtorc1 Regulates the Cap Recruitment Of A Network Of Translamentioning

confidence: 95%

Regulation of global and specific mRNA translation by the mTOR signaling pathway

2015

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Section: Mtorc1 Regulates the Cap Recruitment Of A Network Of Translamentioning

confidence: 95%

Regulation of global and specific mRNA translation by the mTOR signaling pathway

2015

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“…One of these is additional eIF4A for which one might imagine a mechanism (60). The others represent different RNA helicases including DDX3, DDX41, DHX9, and DHX29 (61)(62)(63)(64). These alternate possibilities are extensively reviewed in Parsyan et al (65).…”

Section: Other Complicationsmentioning

confidence: 99%

eIF4F: A Retrospective

Merrick

2015

Journal of Biological Chemistry

148

156

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The original purification of the heterotrimeric eIF4F was published over 30 years ago (Grifo, J. A., Tahara, S. M., Morgan, M. A., Shatkin, A. J., and Merrick, W. C. (1983) J. Biol. Chem. 258, 5804 -5810). Since that time, numerous studies have been performed with the three proteins specifically required for the translation initiation of natural mRNAs, eIF4A, eIF4B, and eIF4F. These have involved enzymatic and structural studies of the proteins and a number of site-directed mutagenesis studies. The regulation of translation exhibited through the mammalian target of rapamycin (mTOR) pathway is predominately seen as the phosphorylation of 4E-BP, an inhibitor of protein synthesis that functions by binding to the cap binding subunit of eIF4F (eIF4E). A hypothesis that requires the disassembly of eIF4F during translation initiation to yield free subunits (eIF4A, eIF4E, and eIF4G) is presented. The Biology of eIF4FThe initial findings in the study of natural mRNA translation reflected the newly discovered m 7 G cap at the 5Ј end of eukaryotic mRNAs (2). mRNAs lacking this structure were translated with less efficiency than mRNAs that contained this structure (3). This unique structure allowed for specific assays or purifications, many established in the laboratory of Dr. Aaron Shatkin with assists from his colleagues. Two of note were the use of m 7 G-Sepharose for affinity purification (4, 5) and the crosslinking of periodate-oxidized mRNAs to proteins (6).The initial application of these methodologies identified two different molecular weight species (about 25,000 and at least 200,000), although the high molecular weight protein contained the small molecular weight component, now known as eIF4E (7). Given the size of several other known translation factors, the question was whether these contained the small molecular weight subunit (notably eIF3 and eIF4B) (8 -11). Ultimate purification of eIF4F indicated that neither of these were correct but that eIF4F would form stable complexes with either, thus being consistent with the eIF4E component tracking with them. At the same time, it was recognized that the 46,000 molecular weight subunit of eIF4F was eIF4A. By physical analysis, eIF4F was a heterotrimeric complex of eIF4A, eIF4E, and eIF4G (1).The next studies were to attempt to identify the functions of the various proteins required specifically for natural mRNA translation (eIF4A, eIF4B, and eIF4F). The characteristics of these three proteins were very different. In the absence of ATP, binding to RNA could only be well demonstrated with eIF4F (Table 1). eIF4A and eIF4F could hydrolyze ATP in the presence of single-stranded RNA, and eIF4B would enhance both of these activities (12). In terms of mechanism, the coupling of the binding of ATP and RNA was realized in recognizing that eIF4A or eIF4F had the ability to unwind duplex RNA. As noted in Table 1, the "strength" of the helicase activity was greater with eIF4F (14).As the ability to determine amino acid sequence from RNA sequence advanced, it was found that there...

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“…We confirmed that DDX3 is required for Rac1 expression at the translational level [12] . The 5' untranslated region (UTR) of Rac1mRNA has a high GC content and may fold into a stable secondary structure; this feature conforms to previously determined DDX3 targets [13][14][15] . Knockdown of DDX3 reduces the translation of a reporter containing the Rac1 5 UTR.…”

Section: Research Highlightmentioning

confidence: 53%

DDX3-mediated translational activation drives β-catenin signaling and cancer cell motility

Chen¹,

Tarn

2015

Can Cell Microenviron

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The DEAD box RNA helicase DDX3 regulates multiple steps in gene expression and also can mediate cell signaling. Dysregulation of DDX3 has been observed in various cancers, and, notably, its mutations are particularly associated with the wingless (Wnt) type of medulloblastoma. DDX3 can promote cell cycle progression, prevent apoptosis, and increase cell migration in some cancerous cells. Detailed mechanisms by which DDX3 modulates cell adhesion and migration and even the epithelial-mesenchymal transition have only just begun to emerge. We recently demonstrated that DDX3 generally modulates cell adhesion and migration properties in various cell lines, essentially via its activity in promoting the translation of Rac1 mRNA. Moreover, our results indicate that DDX3-activated Rac1 translation is required for Wnt-β-catenin signaling and supports the cell adhesion and migration activities of metastatic cancer cells. This DDX3-Rac1-β-catenin pathway suggests a new role for DDX3 in the Wnt type, and perhaps also other types, of medulloblastoma.To cite this article: Hung-Hsi Chen, et al. DDX3-mediated translational activation drives β-catenin signaling and cancer cell motility. Can Cell Microenviron 2014; 1: e392.

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DEAD-box protein DDX3 associates with eIF4F to promote translation of selected mRNAs

Cited by 238 publications

References 59 publications

Regulation of global and specific mRNA translation by the mTOR signaling pathway

Regulation of global and specific mRNA translation by the mTOR signaling pathway

eIF4F: A Retrospective

DDX3-mediated translational activation drives β-catenin signaling and cancer cell motility

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